The AIDS Malignancy Consortium (AMC) was established in 1995 and has been at the forefront of the clinical evaluation of interventions for the treatment and prevention of malignancies in HIV and in studying the biology of cancers in HIV in the context of its clinical trials. Since that time the AMC has conducted 96 clinical trials surveys and laboratory studies involving 3484 patients with HIV-associated cancers and published on a wide variety of topics in AIDS malignancies. Several key scientific findings that emerged from AMC studies have led to improvements in the treatment or management of patients and have helped establish the current standard of care for several of these tumors, including Kaposi's sarcoma, non-Hodgkin's lymphoma, anal cancer and anal intraepithelial neoplasia. In addition, the AMC is a leader in the pharmacokinetic assessment of new targeted cancer therapies in conjunction with antiretroviral therapy, which has helped define safe doses of these drugs when used in combination. The AMC is also conducting clinical trials in HIV-associated cancers in sub-Saharan Africa where the epidemic of HIV and cancer has grown substantially. The participation of many of the key clinical and laboratory researchers in AIDS malignancies in the USA has made the AMC the principal clinical trials group in the world dedicated to improving the treatment and prevention of cancers in this population. We propose to continue and expand our domestic and international clinical trials work in these areas, including the ANCHOR trial, a large randomized controlled study investigating the role of routine anal screening and intervention for high-grade anal squamous intraepithelial lesions for the prevention of anal cancer in HIV, which has rapidly increased in incidence recently.